150 mg Depot Ovules: 1 ovule contains 150 mg micronized econazole nitrate.
Excipients/Inactive Ingredients: 150 mg Depot Ovules: Polygel 371, colloidal anhydrous silica, hard fat, stearyl heptanoate/caprylate.
Pharmacotherapeutic Group: Antiinfectives and antiseptics, excl. combination with corticosteroids, imidazole derivatives. ATC Code: G01A F05.
Pharmacology: Pharmacodynamics: Mechanism of action: Econazole nitrate acts by damaging fungal cell membranes, resulting in increased permeability. Sub-cellular membranes in the cytoplasm are damaged. The site of action is most probably the unsaturated fatty acid acyl moiety of membrane phospholipids.
Pharmacodynamic effects: Microbiology: A broad spectrum of antimycotic activity has been demonstrated against dermatophytes, yeasts and molds. A clinically relevant action against gram-positive bacteria has also been found.
Pharmacokinetics: Absorption: Systemic absorption of econazole is extremely low after vaginal application. Following vaginal application of econazole nitrate cream, about 5% to 7% of the dose was absorbed. Mean peak plasma/serum concentrations of econazole and/or its metabolites were observed 1 to 2 days after dose administration and were approximately 65 ng/mL for the 150 mg Ovule.
Distribution: Econazole and/or its metabolites in the systemic circulation are extensively bound (> 98%) to serum proteins.
Metabolism: Econazole that reaches the systemic circulation is extensively metabolized by oxidation of the imidazole ring, followed by O-dealkylation and glucuronidation.
Excretion: Econazole and metabolites are eliminated in urine and feces.
Toxicology: Non-Clinical Information: Preclinical effects were observed only at exposures considered sufficiently in excess of the maximum human exposure, indicating little relevance to clinical use.
Acute toxicity studies indicate a wide margin of safety with rodent oral LD50 values ranging from >160-463 mg/kg. In repeat dose toxicity studies, at high doses (50 mg/kg/day) the liver was identified as a target organ with minimal toxicity and full recovery.
Neither significant topical toxicity, phototoxicity, local dermal irritation, vaginal irritation nor sensitization was noted. Only mild ocular irritation was noted with a cream formulation.
Carcinogenicity and Mutagenicity: No studies on the carcinogenic potential have been conducted due to the short course of proposed clinical therapy and the absence of any significant potential of econazole to be genotoxic in a way that could lead to initiation or promotion of tumor formation.
In various test systems either no or some limited gene-toxicity effects (structural chromosomal deviations) have been shown. Based on an overall assessment of these data and the indicated route of administration including the resulting minimal systemic exposure to econazole, there is little relevance for clinical use.
Reproductive Toxicology: Results of econazole reproduction studies showed no effects on teratogenicity.
Fertility: Results of econazole reproduction studies showed no effects on fertility.
Pregnancy: Low neonatal survival and fetal toxicity was associated only with maternal toxicity. In animal studies, econazole nitrate has shown no teratogenic effects but was fetotoxic in rodents at maternal subcutaneous doses of 20 mg/kg/day and at maternal oral doses of 10 mg/kg/day. The significance of this in humans is unknown.
GYNO-PEVARYL is indicated for the treatment of vulvovaginal mycoses and mycotic balanitis.
Adult females: 150 mg Depot Ovules: One depot ovule is inserted high into the vagina in the morning and one in the evening. This is best done in the reclining position.
Special populations: Pediatrics (2 to 16 years old): The safety and effectiveness in children has not been established.
Elderly (older than 65 years old): Data are insufficient regarding the use of GYNO-PEVARYL in the elderly (> 65 years old).
Symptoms and signs: Adverse events associated with overdose or misuse of GYNO-PEVARYL are expected to be consistent with adverse reactions already listed in Adverse Reactions.
Treatment: In the event of accidental ingestion, treat symptomatically.
GYNO-PEVARYL is contraindicated in individuals who have shown hypersensitivity to any of its ingredients.
For intravaginal use only. GYNO-PEVARYL is not for ophthalmic or oral use.
The concurrent use of latex condoms or diaphragms with vaginal anti-infective preparations may decrease the effectiveness of rubber contraceptive agents. Therefore products such as GYNO-PEVARYL should not be used concurrently with a diaphragm or latex condom. Patients using spermicidal contraceptives should consult their physician since any local vaginal treatment may inactivate the spermicidal contraceptive.
GYNO-PEVARYL should not be used in conjunction with other internal or external treatment of the genitalia.
If marked irritation or sensitivity occurs, the treatment should be discontinued. Patients with sensitivity to imidazoles have also reported sensitivity to econazole nitrate.
Effects on Ability to Drive and Use Machines: None known.
Pregnancy: Animal studies have shown reproductive toxicity (see Pharmacology: Toxicology: Non-Clinical Information under Actions). Because there is vaginal absorption, GYNO-PEVARYL should not be used in the first trimester of pregnancy unless the physician considers it essential to the welfare of the patient. GYNO-PEVARYL may be used during the second and third trimester if the potential benefit to the mother outweighs the possible risks to the fetus.
Breast-feeding: Following oral administration of econazole nitrate to lactating rats, econazole and/or metabolites were excreted in milk and were found in nursing pups. It is not known whether econazole nitrate is excreted in human milk.
Caution should be exercised when using GYNO-PEVARYL if the patient is breast-feeding.
Fertility: Results of econazole animal reproduction studies showed no effects on fertility (see Pharmacology: Toxicology: Non-Clinical Information under Actions).
Throughout this section, adverse reactions are presented. Adverse reactions are adverse events that were considered to be reasonably associated with the use of econazole nitrate based on the comprehensive assessment of the available adverse event information. A causal relationship with econazole nitrate cannot be reliably established in individual cases. Further, because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Clinical trial data:
The safety of GYNO-PEVARYL Vaginal Ovules was evaluated in 3630 patients who participated in 32 clinical trials. Adverse reactions reported for ≥1% of patients treated with either GYNO-PEVARYL Vaginal Ovules in these studies are shown in Table 1. (See Table 1.)
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Adverse reactions that occurred in <1% of patients treated with either GYNO-PEVARYL Vaginal Ovules in the 32 clinical trials are listed in Table 2. (See Table 2.)
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In addition to the adverse reactions reported during clinical studies and listed previously, the following adverse reactions have been reported during postmarketing experience (Table 3). The frequencies are provided according to the following convention: Very common ≥1/10; Common ≥1/100 and <1/10; Uncommon ≥ 1/ 1000 and <1/100; Rare ≥1/10000 and <1/1000; Very rare <1/10000, including isolated reports.
In Table 3, adverse reactions are presented by frequency category based on spontaneous reporting rates. (See Table 3.)
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Econazole is a known inhibitor of CYP3A4/2C9. Due to the limited systemic availability after vaginal application (see Pharmacology: Pharmacokinetics under Actions), clinically relevant interactions are unlikely to occur, but have been reported with oral anticoagulants. In patients taking oral anticoagulants, such as warfarin or acenocoumarol, caution should be exercised and the anticoagulant effect should be monitored.
Incompatibilities: None known.
G01AF05 - econazole ; Belongs to the class of imidazole derivative antiinfectives. Used in the treatment of gynecological infections.
Depot ovule 150 mg x 2's.